This is the competitive renewal for a grant that has led to several key discoveries in the field of oligodendrocyte cell identity. Based on our previous record of productivity, solid preliminary data and resources and the collaboration with leaders in the field of epigenetics, chromatin and system biology, we propose to continue to elucidate mechanisms of oligodendrocyte differentiation and myelin formation. The proposed experimental plan will impact not only the field of neurobiology, but also address important biological questions with implications for a broad range of disciplines and contribute to the development of novel therapeutic strategies. PUBLIC HEALTH RELEVANCE: Epigenetic mechanisms serve as an interface between the environment and gene expression and they are responsible for the long-lasting changes in nuclear chromatin that define cell identity. We study these mechanisms in oligodendrocyte lineage cells. The goal is to define their potential role for repair of neonatal and adult neuropathologies as well as psychiatric disorders.